Numerous techniques and systems have been developed to enhance drug delivery. Principal objectives include providing therapeutically effective amounts of a drug, sustained release of a drug under conditions that allow sufficient control over the drug's delivery rate, and facile implantation of the drug delivery device.
Some systems employ a polymer drug delivery device in order to achieve such objectives. The use of controlled release polymeric systems is an approach that holds promise for improving the duration and effectiveness of drugs, for both local and systemic action. Micrometer- and nanometer-sized polymeric systems have been used to deliver precise amounts of drugs, including proteins and genes, over prolonged times to local tissues or the systemic circulation following injection. Biodegradable microparticles have been shown to be a suitable delivery vehicle. Furthermore, others have achieved sustained release by temporarily altering the chemical properties of the agent or packaging the agent with excipients or other agents with the polymer.
For polymers used as biocompatible implant materials, their properties, particularly the surface composition, are of great importance. Efforts include introducing biocompatible components into the bulk system and on their surface. Studies described, for example, in J. Colloid Interface Sci., 149:84 (1992) have shown that copolymers with a pendant glucose unit in the bulk or surfaces with covalently bound neutral polysaccharides demonstrate the reduction of platelet adhesion and protein adsorption.
Polymers having pendant sugar moieties known as “glycopolymers” (Bioconj. Chem., 3:256 (1992)) have attracted much interest in recent years, largely as scaffolds for the multivalent display of biologically important carbohydrate molecules. These glycopolymers have been used as potent inhibitors of viral-host cell attachment and leukocyte-endothelial cell adhesion (FEBS, 272:209 (1990); Can. J. Microbiol., 37:233 (1991); J. Am. Chem. Soc., 119:3161 (1997)). Glycopolymers have also been explored as vehicles for targeted drug and gene delivery (J. Hepatology, 21:806 (1994)), and as artificial substrates for cell adhesion (J. Cell Biol., 115:485 (1991)). The suitability of glycopolymers as biocompatible implant materials has been relatively unexplored and is limited to a few examples described, for example, in Microbiol. Chem. Phys., 195:3597 (1994).
Implantable surgical devices such as surgical fasteners, clips, staples, and sutures are typically employed in surgical procedures to hold body tissue together to promote the healing and joining of the tissue. Such surgical devices are often made from synthetic biodegradable or bioerodible polymers. Synthetic absorbable multifilament sutures such as Dexon, Vicryl, and Polysorb, commercially available from Davis & Geck (Danbury, Conn.), Ethicon, Inc. (Somerville, N.J.), and United States Surgical Corporation (Norwalk, Conn.), respectively, are well known in the industry. The advantage of biodegradable devices is that, once implanted, they do not need to be removed by a separate surgical operation since they are degraded and absorbed by the body. Ideally, the surgical device maintains its strength for as long as it takes the body tissues to heal. Thereafter, the device should rapidly degrade and disappear. For example, U.S. Pat. No. 5,889,075 describes a surgical suture fabricated from a copolymer containing dioxanone, trimethylene carbonate and glycolide is treated with gamma radiation to enhance bioabsorbability without adversely effecting handling properties. An example of a highly desirable polymer for use in forming biodegradable sutures is poly(glycolic acid) (PGA). Filaments extruded from PGA are bioabsorbable and biocompatible, and therefore can safely be absorbed into the body after a relatively short time period, making it unnecessary for the sutures to be removed from the patient. One example of an absorbable suture made of a PGA polymer can be found in U.S. Pat. No. 4,621,638.
Several groups have reported the fabrication of fibers with subsequent impregnation of drug by contact with drug containing solutions (Kurtz, 1975; Chkhikvadze et al., 1991). Electrostatic spinning of drug-laden polymer fibers has been reported (Ignatious and Baldoni, 2001; Verreck et al., 2003a; Verreck et al., 2003b; Brewster et al., 2003).
Biodegradable sutures coated with drug, usually antibiotics, can deliver drug, but the thin coat only stores minimal amount of drug. Because of the thin coat, the drug coated suture elutes drug for a short period of time. In addition, after the coating is gone, residual suture remains but does not function to elute drug.
The ability to combine the benefits of drug delivery from a polymeric system with the implementation method of a biodegradable implant such as a suture, fiber, or mesh would provide an improved method for drug delivery in the medical field.